Introduction: Studies have shown that fat lesions follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat lesions at vertebral corners have also been shown to predict development of new syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute both an important measure of treatment efficacy as well as a surrogate marker for new bone formation. The aim of this study was to develop and validate a new scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS), which in contrast to the existing scoring method addresses the localization and phenotypic diversity of fat lesions in patients with axial SpA. Methods: Fat lesions at pre-specified anatomical locations at each vertebral endplate (C2 lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two readers independently evaluated MRIs obtained at two time points for 58 patients (Exercise 1), followed by optimization of scoring methodology and reader calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise 2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs). Results: In Exercise 2, the mean (SD) baseline FASSS score for the two readers was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was 4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class correlation coefficients (ICCs) for status and change scores were excellent (0.96 (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability of change scores was also observed for MRI scans conducted one year apart (ICC 0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both exercises, inter-reader reproducibility for the total FASSS status score improved from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90). Conclusions: FASSS meets essential validation criteria for quantification of a common structural abnormality in clinical trials of axial spondyloarthritis.